Cancer occurs when cell division gets out of control and results from impairment of a DNA repair pathway, the transformation of normal genes into oncogenes or the malfunction of tumor supressor genes. Many different forms of cancer exist. The incidence of these cancers varies but it represents the second highest cause of mortality, after heart disease, in most developed countries.
Bladder cancer is the fifth cancer in term of incidence. It can appear as superficial lesions restricted to the urothelium (Ta and carcinoma in situ (CIS)) or to the lamina propria (T1) or as muscle invasive lesions (T2-T4). Two different pathways of tumour progression have been so far described in bladder cancer, the Ta pathway and the CIS pathway. Ta tumours which constitute 50% of bladder tumours at first presentation are superficial papillary tumour usually of low grade which do not invade the basal membrane. Carcinoma-in-situ (CIS) are also superficial tumour which do not invade the basal membrane but are always of high grade. Ta tumours, despite chirurgical resection associated or not with BCG (Bacillus Calmette-Guerin) therapy, often recur but rarely progress to muscle invasive disease (T2-T4), whereas CIS often progress to T2-T4 tumors. Concerning muscle invasive bladder carcinomas, the standard treatment is cystectomy. Despite this radical treatment, muscle invasive bladder carcinoma remains a deadly disease for most patients.
Up to now, even if many recurrent chromosomal alterations have been described in bladder cancer, only few genes have been demonstrated to be implicated in tumor progression (p53, CDKN2A, RB1, E2F3, FGFR3).
Accordingly, there is a significant need for an appropriate bladder tumor treatment, in particular for new and more effective therapeutic agents.